Dr. Matthew Hill: How Cannabis Impacts Health & the Potential Risks

Dr. Matthew Hill and his peers explore cannabis's effects on the human body, particularly how cannabinoids like THC and CBD, as well as other plant compounds, interact with the body's endocannabinoid system.

Cannabis is a complex plant with over 70 different cannabinoids, including THC and CBD, as well as terpenes that can modulate its effects.

Cannabis has been lauded for its medicinal, spiritual, and recreational uses for centuries. The plant contains multiple molecules called cannabinoids; delta-9-tetrahydrocannabinol (THC) is the most prominent for its psychoactive effects. While THC is known for its intoxicating properties, cannabidiol (CBD) is structurally similar but doesn't produce those effects. It may affect anxiety or mood, however, and is considered psychoactive in a broader sense. There are over 70 additional cannabinoids in cannabis, including the lesser-known cannabigerol, and their effects are mostly unknown.

Terpenes like limonene and pineene also play a role, contributing to the smell and flavor profiles of different cannabis strains. Some terpenes have known biological activity, but their interactions with cannabinoids are not yet fully understood.

Dr. Matthew Hill talks about the “entourage effect,” which suggests that terpenes and minor cannabinoids may influence THC's effects. This remains a complex and relatively unexplored area of cannabis chemistry. Research by scientists like Ryan Vandry and Ziva Cooper is beginning to shed light on how specific terpene compositions might modulate the effects of THC. For example, Vandry's study at Johns Hopkins found that adding limonene could decrease THC-induced anxiety at high doses.

Despite common misconceptions, Hill clarifies that indica and sativa cannabis strains do not have distinct chemical profiles. Nick Giacomis's analysis, which examined thousands of cannabis samples, found no consistent chemical differences between these groupings.

The main psychoactive component is THC, which binds to CB1 receptors and can produce intoxicating effects.

Dr. Matthew Hill asserts that THC is the main substance driving the high from cannabis. THC's potency as a psychoactive component arises from its action on the widespread cannabinoid type 1 receptor (CB1), located throughout the brain. Hill points out that even a trace amount of THC in the brain is sufficient to produce psychoactivity, and emphasizes that products like distillate pens, which contain isolated THC, would have different effects than a more naturally composed cannabis product.

CBD is not intoxicating and may have some therapeutic benefits, but its effects are not well understood at typical dosages.

Contrary to THC, CBD doesn’t act like an intoxicant and is not typically perceptible when ingested. There’s skepticism around its efficacy at doses commonly found in commercial products, and only pediatric epilepsy has shown some benefit at high dosage levels in clinical studies. Hill suggests that many reported effects of CBD, especially at low dosages, could potentially be attributed to placebo effects.

The endocannabinoid system regulates homeostasis in the body through tonic and phasic release of endocannabinoids like anandamide and 2-AG.

Dr. Hill explained that the endocannabinoid system, primarily involving the endocannabinoids anandamide and ...

The podcast covers a variety of topics regarding the effects of THC and CBD on processes such as hunger, memory, and anxiety management.

Cannabis use can produce a range of subjective effects, including euphoria, altered perceptions, and changes in appetite and time perception.

The subjective effects of cannabis are highly dependent on dose, with low doses potentially reducing anxiety and higher doses potentially increasing anxiety.

Matthew Hill describes the intoxicating effects of cannabis, including a sense of euphoria, altered feeding behavior, and sometimes a dissociative state that changes awareness and perception. Another effect noted by Hill and Andrew Huberman is altered time perception, where users feel that time has elongated. Hill points out the term "munchies," explaining that THC may increase the reward value of food, thus enhancing appetite.

The discussion highlights the variability in individual experiences when consuming cannabis, often influenced by the type of product and its chemical composition. It is suggested that low doses of THC can reduce anxiety, while higher doses may trigger it. The expectancy bias plays a significant role in this, as expectations can influence the perceived effects. Hill suggests that the anxiolytic effect observed in many regular cannabis users might not strongly carry over to clinical trial settings.

Chronic cannabis users can develop tolerance and may require higher doses to achieve the desired effects. Hill notes that even heavy users can experience a high from lower potency products, suggesting that tolerance to cannabis may not be completely linear. Regular use of high THC products prompts biological changes that differ from the effects of moderate THC intake from smoking the plant.

Chronic cannabis use can lead to tolerance, with users reporting the need to consume more to achieve the desired effects.

Hill explains that chronic cannabis use, especially with high-potency concentrates, can lead to tolerance, requiring users to consume more to achieve their desired intoxication level. This biological response to the heavy influx of THC is comparable to other forms of substance dependence, with some users becoming irritable without access to cannabis.

Cannabis can also affect various physiological processes, including cardiovascular function, cognition, and sleep.

Cannabis use may transiently impair memory and cognitive function, but the long-term effects are less clear.

The podcast discusses the short-term effects of cannabis on memory processing, noting that while a user is intoxicated, there can be memory recall deficits. The long-term impact on memory ...

Recent discussion among researchers like Huberman and Hill has shed light on the therapeutic potential of cannabis and its components in treating various medical conditions, such as epilepsy, chronic pain, and PTSD, though the field's understanding is limited by a lack of extensive clinical trials.

Cannabis or its components may have some therapeutic benefits for conditions like epilepsy, chronic pain, and PTSD.

CBD has shown promise in treating certain types. of epilepsy, particularly in children with Dravet syndrome.

Huberman talks about a strain of cannabis called Charlotte's Web, which is rich in CBD and has become well-known for its potential to help with epileptic seizures, specifically in pediatric epilepsy such as Dravet syndrome. Studies by neurologist Elizabeth Teal and others have presented compelling data on CBD's efficacy, influencing the rescheduling of CBD. These trials often highlight the use of very high doses of CBD, which have been relatively effective at reducing frequent seizures in some children. Hill adds to this by mentioning GW Pharmaceuticals' development of a pharmaceutical version of CBD that, when taken with a fatty meal, shows dramatically enhanced bioavailability, suggesting that the presence of dietary fat might aid CBD absorption.

Some evidence suggests cannabis or its synthetic derivatives may help reduce PTSD-related nightmares, but the research is limited.

Matthew Hill discusses the potential benefits of cannabis for individuals suffering from PTSD, especially regarding the suppression of nightmares. Some veterans in a study by the Canadian military reported that using THC before bed helped eliminate nightmares. This is significant for PTSD treatment, as it may reduce re-experiencing of trauma. Additionally, studies using the synthetic THC variant [restricted term] have shown a reduction in nightmares in a treatment-resistant PTSD population, although it should be noted that these trials, such as a double-blind placebo-controlled crossover study, have been limited by their small sample sizes. Hill acknowledges the absence of data pointing to a long-term improvement in disease prognosis but notes that if cannabis reduces sensitization, it may still offer some prognostic benefit for ...

Various experts discuss the complexities and potential risks of cannabis use, particularly concerning mental health, physiological effects, and the methodological challenges in both research and regulation of the substance.

Cannabis use may increase the risk of developing psychosis or exacerbate symptoms in individuals predisposed to conditions like schizophrenia.

The relationship between cannabis use and psychosis is complex and unclear

Andrew Huberman and Matthew Hill discuss high-profile papers that suggest a potential increase in long-term psychosis risk for high THC cannabis users, particularly those who begin using at a young age, which may impact males more significantly. While Matthew Hill acknowledges that acute psychotic episodes induced by THC are rare, occurring in less than 5% of cases, he emphasizes the complexity of the relationship, noting that the predisposition to psychosis plays a role.

Hill also critically assesses the idea that high-potency cannabis is solely responsible for increased schizophrenia risk. He challenges this by noting that even when cannabis potency was low, such as in a foundational 1987 Lancet study from Sweden, there was an association with schizophrenia. Hill posits that predisposed individuals have a biological tendency to seek potent cannabis regardless of the availability, which complicates any direct cause-effect relationship between cannabis use and psychosis.

Regular cannabis use during adolescence as a risk factor

The conversation suggests that there might be a link between adolescent use of high THC cannabis and the lasting risk of psychosis, with developing brains being particularly susceptible. Hill compares adolescent use rates and schizophrenia prevalence between places like Canada, the U.S., and Scandinavian countries, questioning the causality since schizophrenia rates have not notably increased following cannabis legalization.

Cannabis use may also pose risks to cardiovascular health and is associated with a rare condition called cyclic vomiting syndrome.

The cardiovascular effects of cannabis remain not well understood. However, Matthew Hill expresses that individuals with cardiovascular problems should avoid cannabis due to emerging evidence hinting at possible risks, though he refrains from stating explicit harms due to limited definitive data.

Additionally, Hill explains cyclic vomiting syndrome ...